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Drug platforms

Chimeric antigen receptors (CARs) that require dual-antigen binding for activation

T cells engineered to express a CAR and a chimeric co-stimulatory receptor could enhance the tumor specificity of targeted T cell therapies. T cells expressing CARs can trigger a tumor antigen-specific immune response but also can cause toxicity if the targeted antigen is not exclusively expressed by tumor cells. To increase specificity, T cells were engineered to carry a CAR that induces T cell activation only when a second co-stimulatory receptor engages with another tumor-specific antigen. In a mouse model of prostate cancer, T cells engineered to bind both prostate stem cell antigen (PSCA) and prostate-specific membrane antigen (PSMA; FOLH1; GCPII) decreased the growth of PSCA+/PSMA+ tumors but not the growth of tumors expressing only one of the two antigens. Next steps include developing additional strategies to increase the safety of the T cell therapy.

SciBX 6(2); doi:10.1038/scibx.2013.46
Published online Jan. 17, 2013

Patent application filed; available for licensing

Kloss, C.C. et al. Nat. Biotechnol.; published online Dec. 16, 2012;
Contact: Michel Sadelain, Memorial Sloan-Kettering Cancer Center, New York, N.Y.